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Drug may limit impact of bad memories: study

The Canadian Press
Published Friday, May 27, 2011 8:08AM EDT

A Canadian study suggests a drug used to decrease stress hormone levels may also limit the long-term impact of bad memories, a finding that could potentially benefit individuals who have suffered psychological trauma.

Lead author Marie-France Marin, a doctoral student at the University of Montreal, said researchers knew there was a close link between memory and cortisol, a stress hormone involved in memory recall.

"We knew that lowering cortisol levels at the time of learning a new event will decrease the formation of that memory," said Marin, based at the Centre for Studies on Human Stress of Louis-H. Lafontaine Hospital. "However, for a very long time, we thought that any effect on memory after it has stabilized in the brain would be temporary."

Marin said previous studies have challenged the theory memory isn't changeable by demonstrating that each time an already-acquired memory is retrieved, it makes the memory active again in the brain.

"At the time of reactivation, we can act again on that memory trace in order to change it in a long-lasting manner, so basically we have a second window of opportunity to change memories."

Marin and Dr. Sonia Lupien, who directed the research, set out to see what would happen if cortisol was lowered at the time a memory was recalled. They looked at determining whether memory would return to normal or if there would be a long-lasting effect.

Researchers at the Centre for Studies on Human Stress conducted a small study involving use of the drug metyrapone, which decreases cortisol levels.

Marin said metyrapone is typically administered to people with Cushing's syndrome, a metabolic disorder in which the body produces too much cortisol or when large doses of corticosteroid drugs are used for an extended period.

The 33 men who took part in the study had no previous history of trauma. They were shown a slide show of 11 images with narration: the first four and final three slides were neutral, while the remaining four were negative. Marin said it depicted the story of little girl visiting her grandparents who decides to build a bird house. At some point her hand gets injured, and the mutilated hand with blood is seen.

Three days later, the men were placed into three groups: one received a single dose of metyrapone, a second was given a double dose and a third received a placebo. The men were then asked to recall the story, and their memory performance was evaluated four days later.

"When everyone's cortisol levels are equivalent because the drug has cleared out from the body, the memory trace is still lower in people who had received the metyrapone," said Marin. "The effect is specific to the negative information, so it leaves neutral memories unaffected."

Marin said the research shows that recalling information under the influence of the drug when cortisol levels are lowered will result in less emotional memory.

"Negative information would be decreased in these people compared to the placebo group," she said,

The greatest impact was observed in the men who took the double dose of metyrapone, spaced three hours apart. Marin said she doesn't necessarily think the added dose makes cortisol levels lower than a lone dose; but since the doses need to be administered a certain time apart, the duration of low cortisol levels is longer in the double dose.

"Maybe it's important that you have low levels for a long time to have a lasting effect on memory," she said.

Metyrapone is no longer being commercially produced, but Marin said other compounds that decrease cortisol levels also could be tested.

"It would be interesting to determine if the effect is specific to metyrapone in this specific path or whether the goal is just to have low cortisol levels and the outcome is the same," she said. "This needs to be tested in future studies."

Marin said the findings could potentially be applied to patients suffering from post-traumatic stress disorder, who are typically treated with therapy and antidepressants.

"We know the therapy is very useful for PTSD patients. However, for some people, it doesn't seem to be optimal; for some, it doesn't work at all," Marin said.

She said coupling therapy with pharmacology could prove beneficial to those patients.

"In therapy, you're recalling the traumatic event, you're recalling what happened, so if you do this recall under the influence of metyrapone, this could potentially reduce the traumatic memory trace," she said. "This could open the way for therapy so you can then more easily deal with your feelings and emotions."